Treatment of heart failure with preserved ejection fraction: have we been pursuing the wrong paradigm?

Abstract

Heart failure with preserved ejection fraction (HF-PEF) is the clinical syndrome of heart failure associated with normal or near-normal systolic function. Because inhibition of the adrenergic and renin-angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these same therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of significant benefit with neurohormonal antagonism in HF-PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure as we traditionally think of it is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

FIGURE 1.

Mode of death of patients in trials of heart failure with preserved ejection fraction. Left, I-PRESERVE = Irbesartan in Heart Failure with Preserved Ejection Fraction Study. Right, CHARM-Preserved = Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity. Data from Circulation.

FIGURE 2.

Criteria to diagnose heart failure with normal left ventricular ejection fraction (HFNEF), referred to as heart failure with preserved ejection fraction in the current study, as per the consensus statement by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Ad = duration of mitral valve atrial wave flow; Ard = duration of reverse pulmonary vein atrial systole flow; b = constant of left ventricular chamber stiffness; BNP = brain natriuretic peptide; DT = deceleration time; E = early mitral valve flow velocity; E′= early TD lengthening velocity; E/A = ratio of early (E) to late (A) mitral valve flow velocity; LAVI = left atrial volume index; LVEDP = left ventricular end-diastolic pressure; Echo = echocardiography; LVEDVI = left ventricular end-diastolic volume index; LVEF = left ventricular ejection fraction; LVMI = left ventricular mass index; mPCW = mean pulmonary capillary wedge pressure; NT-proBNP = N-terminal pro-brain natriuretic peptide; τ = time constant of left ventricular relaxation; TD = tissue Doppler. From Eur Heart J, with permission.